Maintenance Tyrosine Kinase Inhibitors Following Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia: A Center for International Blood and Marrow Transplant Research Study |
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| Affiliation: | 1. Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, Massachusetts;2. Scripps Blood & Marrow Transplant Program, Scripps Green Hospital, La Jolla, California;3. Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin;4. Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin;5. Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom;6. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California;7. Department of Hematology, Academische Ziekenhuis, Maastricht, The Netherlands;8. Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio;9. Markey Cancer Center, University of Kentucky, Lexington, Kentucky;10. Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota;11. Tom Baker Cancer Centre, Calgary, Alberta, Canada;12. Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City, Kansas;13. Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan;14. Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, Minnesota;15. Department Clinical Haematology and Bone Marrow Transplantation, Royal Melbourne Hospital, Victoria, Australia;16. Stanford Health Care, Stanford, California;17. Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida;18. Blood and Marrow Transplantation Program and Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York;19. Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia''s Children''s Hospital, The University of British Columbia, Vancouver, BC, Canada;20. Division of Cancer Epidemiology & Genetics, NIH-NCI Clinical Genetics Branch, Rockville, Maryland;21. Department of Medicine, University of Rochester Medical Center, Rochester, New York;22. Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, Wisconsin;23. Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas;24. Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota;25. Department of Oncology, Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;26. Division of Hematology, Oncology and Blood & Marrow Transplantation, Children''s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California;27. The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, Georgia;28. Department of Hematology, Inselspital, Bern University Hospital, Switzerland;29. Interdisciplinary Clinic for Stem Cell Transplantation, University Cancer Center Hamburg, Hamburg, Germany;30. Seidman Cancer Center, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio;31. Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;32. Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden;33. Department of Hematology, CHU Grenoble Alpes, Grenoble, France;34. Carolinas Medical Center Blumenthal Cancer Center Stem Cell Transplant Program, Levine Cancer Institute, Charlotte, North Carolina;35. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;36. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland;37. Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel;38. Division of Hematology and Oncology, Department of Medicine, UMass Memorial Medical Center, Worcester, Massachusetts;39. Department of Medicine, University of Miami, Miami, Florida;40. Department of Hematology & Oncology, National Cancer Research Center East, Chiba, Japan;41. Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida;42. Division of Hematology & Oncology, Department of Medicine, Shands HealthCare and University of Florida, Gainesville, Florida;43. Center of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts;44. Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas |
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| Abstract: | It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myelogenous leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML who underwent transplantation between 2007 and 2014 and received maintenance TKI following HCT (n = 89) compared with no TKI maintenance (n = 301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy before HCT. The majority of patients had a disease status of first chronic phase at HCT (n = 240; 62%). The study was conducted as a landmark analysis, excluding patients who died, relapsed, had chronic graft-versus-host disease, or were censored before day +100 following HCT. Of the 89 patients who received TKI maintenance, 77 (87%) received a single TKI and the other 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n = 50), imatinib (n = 27), and nilotinib (n = 27). As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%; P = .11), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; P = .65), or overall survival (maintenance, 61% versus no maintenance, 57%; P = .61) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation. In conclusion, our data from this day +100 landmark analysis do not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes. The optimal approach to TKI administration in the post-transplantation setting in patients with CML remains undetermined. |
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